ENANTIOSELECTIVE SYNTHESIS OF BIS(GAMMA-BUTYROLACTONES) - THEIR OXIDATIVE-DEGRADATION TO TETRAOLS AS A KEY STEP IN STEREOSELECTIVE SYNTHESES OF 1,3,5,7,9-PENTAOL SYNTHONS FOR POLYHYDROXYLATED NATURAL-PRODUCTS

The syntheses of two enantiopure skipped-chain pentaol building blocks 51 and 56 are described. They are based on a strategy which derives 1 ,3,7,9-tetraols from bis(gamma-butyrolactones). Two equivalents of gam ma-lactone 17, readily available from L-glutamic acid, and one equival ent of the diiodoisobutene 22 furnished bis(gamma-butyrolactone) trans ,trans-21 stereoselectively in a single step. The same lactone, combin ed in a 2:1 ratio with the dibromoisobutene derivative 18, led in four steps and with good stereocontrol to the isomeric bis(gamma-lactone) cis,trans-21. On the basis of the H-1- and C-13-NMR spectral data of t hese and other lactones it was possible to distinguish 1,3-cis- and 1, 3-trans-disubstituted gamma-lactones. Each of the bislactones was subj ect to a Criegee rearrangement of derived bis(peroxosulfonates) to giv e the diastereomerically pure 1,3,7,9-tetraols 26 and 31. The configur ation of these tetraols was proven by the C-13-NMR shifts of the corre sponding bis(acetonides) 27 and 32. Ozonolytic cleavage of the C=C bon d of 27, reduction of the obtained ketone 28 to alcohol 29, acetonide rearrangement under thermodynamic control (--> 30), and fuctionalizati on of the liberated hydroxy group delivered the end group-differentiat ed 1,3,5,7,9-pentaol building block 51. It represents a segment of the polyol parts of the antibiotics roxaticin (52) and mycoticin (53). Th e oxidative cleavage of the C=C bond of bis(acetonide) 32 and chelatio n-controlled reduction of the resulting ketone 33 with Zn(BH4)(2) furn ished after acetonide migration and functionalization of the unprotect ed hydroxy group the all-syn-configured 1,3,5,7,9-pentaol building blo ck 56. The latter compound should provide an entry into total synthese s of the naturally occurring poly(methyl ethers) 57 and 58.